Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: synthesis, stereochemistry, and NMR line broadening.

Abstract

The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture combined with NMR and molecular modeling studies proved that natural lyngbyastatin 1 was only one Ibu epimer rather than a mixture of both and that the configuration of this epimer in the Ibu unit was R. The substance isolated with lyngbyastatin 1 was Ibu-epidolastatin 12. The extreme broadness in the proton NMR spectra of lyngbyastatin 1 and Ibu-epidolastatin 12 was exchange broadening due to rotation about the Ibu-Ala amide bond. It was a consequence of (1) a small energy difference between the cis and trans forms of this bond, (2) a substantial difference in conformation between these forms, and (3) a lowered barrier between them compared to most amide bonds (due to steric hindrance). The synthetic lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture had significant activities against cancer cells and in stimulating actin polymerization, but was less active than dolastatin 11 in all assays.

• Authors: Ruoli Bai, Robert B Bates, Ernest Hamel, Richard E Moore, Pichaya Nakkiew, George R Pettit, Bilal A Sufi
• Journal: Journal of natural products (J Nat Prod) Vol. 65 Issue 12 Pg. 1824-9 (Dec 2002) ISSN: 0163-3864 [Print] United States
• PMID: 12502322 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Actins
• Antineoplastic Agents
• Depsipeptides
• Ibu-epilyngbyastatin 1
• Oligopeptides
• Peptides, Cyclic
• dolastatin 11
• lyngbyastatin 1

Topics

• Actins (antagonists & inhibitors, drug effects)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Depsipeptides
• Drug Screening Assays, Antitumor
• Humans
• Lung Neoplasms
• Male
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Oligopeptides (chemical synthesis, chemistry, pharmacology)
• Peptides, Cyclic (chemical synthesis, chemistry, pharmacology)
• Prostatic Neoplasms
• Seaweed (chemistry)
• Stereoisomerism
• Structure-Activity Relationship
• Tumor Cells, Cultured (drug effects)